Curcumin is a phytochemical compound with anticancer activity. Although curcumin has substantial pharmacological effect against various cancers, the low solubility of curcumin has hindered its development. For an organic solvent-free injectable formulation, we encapsulated curcumin in various liposomes. Due to its lipophilic property, curcumin was placed in the membrane region of liposomes. Curcumin was stably encapsulated in all formulations tested in this study. The cellular uptake of curcumin delivered in liposomal formulations or free form was measured in K562 human leukemia cell lines using a flow cytometry and MTT viability assay, respectively. Although all the liposomes could solubilize curcumin, the cellular levels and the anticancer effects of liposomal curcumin varied with the composition of liposomes. Moreover, liposomal curcumin down-regulated the expression of Notch-1, the molecule involved in the carcinogenesis, to the similar extent to free curcumin dissolved in dimethyl sulfoxide. These results warrant the development of liposomal curcumin as an injectable formulation for leukemia treatment.

The aim of this study was to investigate the effect of deformable liposomes with sodium cholate on the skin permeation and skin deposition of arbutin, a hydrophilic skin-whitening agent. Various compositions of liposomes were prepared by the extrusion method. Particle size distribution and entrapment efficiency were determined by the laser light scattering and the gel permeation chromatography, respectively. The in vitro rat skin permeation and deposition of arbutin in various skin layers were investigated using the Keshary-Chien diffusion cells at . The average particle size of the deformable liposomes ranged from 217.4 to 117.4 nm, depending on the composition. The entrapment efficiency was dependent on surfactant concentration and loading dose of arbutin. The permeation rate of 5% arbutin in deformable liposomes was , and was not significantly different from 5% arbutin aqueous solution . The deposition of arbutin was and in stratum corneum layer and epidermis/dermis layer, respectively, after 12 h of permeation study. These results are consistent with several earlier studies for the localization effect of liposomal formulations in stratum corneum, and demonstrated the feasibility of the deformable liposomes as a promising carrier for the skin deposition of hydrophilic skin-whitening compounds.

Poloxamer-based hydrogel formulation for the topical delivery of ascorbic acid(AsA) was prepared and the effect of limonene on AsA skin permeation and localization was evaluated. In vitro rat skin permeation study, the AsA skin permeation of limonene-containing hydrogel was about 3 to 5 fold higher than control hydrogel. However the amount of permeated AsA was independent to the concentration of limonene. On the other hand the localized amount of AsA after 2 h increased proportion to the content of limonene. The increase in the ratio of localized AsA() to permeated AsA() was attributed to the limonene's ability of making polar pathway within stratum corneum by interacting on lipid domain of the skin and the AsA's hydration effect on the stratum corneum and effect on the protein domain of the skin.

The multicellular layers(MCL) of human cancer cells is a three dimensional(3D) in vitro model for human solid tumors which has been used primarily for the assessment of avascular penetration of anti-cancer drugs. For anti-cancer drugs with penetration problem, MCL represents a good experimental model that can provide clinically relevant data. Calcein-AM is a fluorescent dye that demonstrates the cellular vitality in a graded manner in cancer cell culture system. In the present study, we evaluated the use of calcein-AM for determination of anti-proliferative activity of anti-cancer agents in MCL model of DLD-1 human colorectal cancer cells. Optical sectioning of confocal imaging was compromised with photonic attenuation and penetration barrier in the deep layers of MCL. By contrast, fluorescent measurement on the cryo-sections provided a feasible alternative. Cold pre-incubation did not enhance the calcein-AM distribution to a significant degree in MCL of DLD-1 cells. However, the simultaneous determination of drug penetration and cellular vitality appeared to be possible in drug treated MCL. In conclusion, these data suggest that calcein-AM can be used for the simultaneous determination of drug-induced anti-proliferative effect and drug penetration in MCL model.

Silymarin showed P-glycoprptein(P-gp) inhibitory activity as much as verapamil, a well-known P-gp inhibitor, by decreasing value of daunomycin(DNM)(), increasing the DNM accumulation(), and decreasing DNM efflux(), concurrently. In this study, we clarified the mechanism of action of silymarin for P-gp inhibitory function. First, silymarin may bind to the ATP-binding site and thus, prevent ATP hydrolysis. Second, the P-gp inhibitory activity of silymarin is not related to changing the cellular P-gp level. Third, the cytotoxicity of silymarin was increased in the presence of verapamil, reflecting that silymarin is a competent P-gp substrate against verapamil in the P-gp-overexpressed adriamycin-resistant MCF-7 breast cancer(MCF-7/ADR) cells. Conclusively, silymarin had the P-gp inhibitory activity through the action of competent binding to the P-gp substrate-binding site. Therefore, silymarin can be a good candidate for safe and effective MDR reversing agent in clinical chemotherapy by administering concomitantly with anticancer drugs.

Albuterol, a selective -adrenergic receptor stimulant, has been introduced as a potent bronchodilator for patients with bronchial asthma, chronic obstructive bronchial disease, chronic bronchitis and pulmonary emphysema. The percutaneous permeation of albuterol sulfate was investigated in hairless mouse skin in vitro with and without pretreatment with enhancers. The enhancing effects of ethanol and various penetration enhancers such as terpenes, non-ionic surfactants, pyrrolidones, and fatty acids on the permeation of albuterol sulfate were evaluated using Franz diffusion cells. Among terpenes studied, 1,8-cineole was the most effective enhancer, which increased the permeability of albuterol sulfate approximately 33-fold compared with the control without enhancer pretrement, followed by d-limonene with enhancement ratio of 21.79. 2-Pyrrolidone-5-carboxylic acid increased the permeability of albuterol sulfate approximately 5.5-fold compared with the control. Other pyrrolidones tested showed only slight permeability enhancing effect with enhancement ratio less than 2.8. Nonionic surfactants showed moderate enhancing effects. Lauric acid increased the permeability of albuterol sulfate approximately 30-fold with decreasing the lag time from 2.85 to 0.64 hr. Oleic acid and linoleic acid showed enhancement ratio of 24.55 and 22.91, respectively. These findings would allow a more rational approach for designing formulations for the transdermal delivery of albuterol sulfate and similar drugs.

A rapid, selective and sensitive reverse-phase HPLC methods for the determination of atenolol and chlorthalidone in human serum and whole blood were validated, and applied to the pharmacokinetic study of atenolol and chlorthalidone combination therapy. Atenolol and an internal standard, pindolol, were extracted from human serum by liquid-liquid extraction, and analyzed on a -Bondapak C18 column in a mobile phase of methanol-0.01 M potassium dihydrogenphosphate(30:70, v/v, adjusted to pH 3.5) and fluorescence detection(emission: 300 nm, excitation: 224 nm). Chlorthalidone and an internal standard, probenecid, were extracted form human whole blood by liquid-liquid extraction, and analyzed on a Luna C18 column in a mobile phase of acetonitrile containing 77% 0.01 M sodium acetate and UV detection at 214 nm. These analysis were performed at three different laboratories using the same quality control(QC) samples. The chromatograms showed good resolution, sensitivity, and no interference by human serum and whole blood, respectively. The methods showed linear responses over a concentration range of 10-1,000 ng/mL for atenolol and 0.05-20 for chlorthalidone, with correlation coefficients of greater than 0.999 at all the three laboratories. Intra- and inter-day assay precision and accuracy fulfilled international requirements. Stability studies(freeze-thaw, short-, long-term, extracted sample and stock solution) showed that atenolol and chlorthalidone were stable. The lower limit of quantitation of atenolol and chlorthalidone were 10 ng/mL and 0.05 , respectively, which was sensitive enough for pharmacokinetic studies. These methods were applied to the pharmacokinetic study of atenolol and chlorthalidone in human volunteers following a single oral administration of Hyundai tablet(atenolol 50 mg and chlorthalidone 12.5 mg) at three different laboratories.

This study was designed to prepare an animal model for partial thickness bum wound which can be employed for testing topical therapy. We first evaluated whether rabbit ear and mouse back skin wound model could differentiate the wound healing process in terms of degree of re epithelialization, required days for complete wound closure, presence of scarring. degree wet bum were prepared on mouse back skin and rabbit ear by applying 5 mL hot water() for 7 see followed by 5 mL ice-cold 0.5% acrynol solution for cooling and disinfecting the inflicted area. After removing the dead epidermis layer at 24 hr, tested dressings were applied for specified time and wound progression was investigated. In mouse model, wound contraction was the primary wound closing mechanism, which is quite different from human wound healing process. In rabbit ear model, epidermal regeneration was the major wound healing process rather than wound contraction and the difference in wound healing property among tested dressings could be clearly demonstrated. A rabbit ear model could differentiate the wound progression among open, occluded and epidermal growth factor(EGF) treated wound. Four sites of circular wound(diameter: 1 cm) on the anterior part of rabbit ear could be employed for the comparative wound healing study. For obtaining reproducible bum wound, degree of bum depth and bum sites should be carefully controlled in addition, employing rabbits of same strain and weight. The result suggests that rabbit ear could be employed as a reliable and human-resembled wound model.

The purpose of the present study was to evaluate the bioequivalence of two zolpidem tartrate tablets, Stilnox tablet(Sanofi-aventis Korea, reference product) and Zanilo tablet(ChoDang Pharm Co., Ltd., Korea, test product), according to the guidelines of Korea Food and Drug Administration(KFDA). After adding an internal standard(cimetropium), 250 plasma samples were extracted using 1.3 mL of ethyl acetate. Extracted compounds were analyzed by HPLC with triple-quadrupole mass spectrometry. This method for determination of zolpidem is proved accurate and reproducible with the limit of quantitation of 1 ng/mL in human plasma. Twenty-four healthy male Korean volunteers received each medicine at the zolpidem tartrate dose of 10 mg in a crossover study. There was one-week washout period between the doses. Plasma concentrations of zolpidem were monitored for over a period of 8 hr after the administration. (the area under the plasma concentration-time curve) was calculated by the linear trapezoidal rule. (maximum plasma drug concentration) and (time to reach ) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed and . No significant sequence effect was found for all of the bio-availability parameters indicating that the crossover design was properly performed. The 90% confidence intervals for the log transformed data were acceptable range of log 0.8 to log 1.25(e.g., log 0.92-log 1.06 for , log 0.96-log 1.13 for ). The major parameters, and met the criteria of KFDA for bioequivalence indicating that Zanilo tablet is bioequivalent to Stilnox tablet.